RU2443698C2 - Конденсированное замещенное производное аминопирролидина - Google Patents
Конденсированное замещенное производное аминопирролидина Download PDFInfo
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- RU2443698C2 RU2443698C2 RU2009129975/04A RU2009129975A RU2443698C2 RU 2443698 C2 RU2443698 C2 RU 2443698C2 RU 2009129975/04 A RU2009129975/04 A RU 2009129975/04A RU 2009129975 A RU2009129975 A RU 2009129975A RU 2443698 C2 RU2443698 C2 RU 2443698C2
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- SBMSLRMNBSMKQC-UHFFFAOYSA-N pyrrolidin-1-amine Chemical class NN1CCCC1 SBMSLRMNBSMKQC-UHFFFAOYSA-N 0.000 title description 20
- 150000001875 compounds Chemical class 0.000 claims abstract description 275
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 202
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 81
- 125000004122 cyclic group Chemical group 0.000 claims abstract description 79
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 71
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 48
- 125000001153 fluoro group Chemical group F* 0.000 claims abstract description 47
- 230000036961 partial effect Effects 0.000 claims abstract description 46
- 150000003839 salts Chemical class 0.000 claims abstract description 37
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims abstract description 36
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 35
- 239000003814 drug Substances 0.000 claims abstract description 34
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 27
- 239000003242 anti bacterial agent Substances 0.000 claims abstract description 24
- 230000000844 anti-bacterial effect Effects 0.000 claims abstract description 24
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 21
- 125000001309 chloro group Chemical group Cl* 0.000 claims abstract description 21
- 125000002619 bicyclic group Chemical group 0.000 claims abstract description 20
- 208000015181 infectious disease Diseases 0.000 claims abstract description 19
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims abstract description 16
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 16
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 12
- 125000006413 ring segment Chemical group 0.000 claims abstract description 9
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims abstract description 4
- 229940124597 therapeutic agent Drugs 0.000 claims abstract description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 17
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 15
- 239000004480 active ingredient Substances 0.000 claims description 4
- -1 6-amino-3,5-difluoropyridin-2-yl group Chemical group 0.000 abstract description 198
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 abstract description 22
- 230000000694 effects Effects 0.000 abstract description 17
- 241000894006 Bacteria Species 0.000 abstract description 8
- 230000035945 sensitivity Effects 0.000 abstract description 7
- 239000000126 substance Substances 0.000 abstract description 7
- 239000003795 chemical substances by application Substances 0.000 abstract description 6
- 238000005859 coupling reaction Methods 0.000 abstract description 4
- 229940072132 quinolone antibacterials Drugs 0.000 abstract description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 abstract 1
- 230000008878 coupling Effects 0.000 abstract 1
- 238000010168 coupling process Methods 0.000 abstract 1
- 239000011737 fluorine Substances 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 450
- 239000000243 solution Substances 0.000 description 298
- 239000000203 mixture Substances 0.000 description 222
- 125000001424 substituent group Chemical group 0.000 description 219
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 210
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 169
- 238000006243 chemical reaction Methods 0.000 description 169
- 230000002829 reductive effect Effects 0.000 description 169
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 147
- 125000000217 alkyl group Chemical group 0.000 description 146
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 139
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 126
- 239000002904 solvent Substances 0.000 description 124
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 120
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 114
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 107
- 125000003277 amino group Chemical group 0.000 description 94
- 238000005160 1H NMR spectroscopy Methods 0.000 description 87
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 86
- 125000005843 halogen group Chemical group 0.000 description 85
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 84
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 81
- 239000012044 organic layer Substances 0.000 description 81
- 125000006239 protecting group Chemical group 0.000 description 78
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 74
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 70
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 68
- 125000003545 alkoxy group Chemical group 0.000 description 66
- 238000010898 silica gel chromatography Methods 0.000 description 66
- 238000001914 filtration Methods 0.000 description 63
- 239000012267 brine Substances 0.000 description 59
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 59
- 239000007787 solid Substances 0.000 description 58
- 239000000706 filtrate Substances 0.000 description 56
- 238000000605 extraction Methods 0.000 description 55
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 52
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 45
- 238000001816 cooling Methods 0.000 description 40
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 38
- 239000003054 catalyst Substances 0.000 description 37
- 239000012230 colorless oil Substances 0.000 description 36
- 239000003921 oil Substances 0.000 description 36
- 125000000753 cycloalkyl group Chemical group 0.000 description 35
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 34
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 34
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 30
- 125000003342 alkenyl group Chemical group 0.000 description 28
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 27
- 229910052739 hydrogen Inorganic materials 0.000 description 27
- 230000003287 optical effect Effects 0.000 description 27
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 27
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 26
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 26
- 229910052799 carbon Inorganic materials 0.000 description 26
- 125000004093 cyano group Chemical group *C#N 0.000 description 26
- 239000001257 hydrogen Substances 0.000 description 26
- 238000000926 separation method Methods 0.000 description 26
- 238000003756 stirring Methods 0.000 description 26
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 25
- 239000010410 layer Substances 0.000 description 25
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 24
- 230000015572 biosynthetic process Effects 0.000 description 24
- 239000011541 reaction mixture Substances 0.000 description 23
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 22
- 239000000543 intermediate Substances 0.000 description 22
- 125000004414 alkyl thio group Chemical group 0.000 description 21
- 238000003786 synthesis reaction Methods 0.000 description 21
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 20
- 125000001072 heteroaryl group Chemical group 0.000 description 20
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 19
- 229940079593 drug Drugs 0.000 description 19
- 229910052736 halogen Inorganic materials 0.000 description 19
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 19
- 235000019341 magnesium sulphate Nutrition 0.000 description 19
- 238000000034 method Methods 0.000 description 19
- 238000010992 reflux Methods 0.000 description 19
- 239000002253 acid Substances 0.000 description 18
- 150000001721 carbon Chemical group 0.000 description 18
- 150000001412 amines Chemical class 0.000 description 17
- 239000002585 base Substances 0.000 description 17
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 17
- 239000013522 chelant Substances 0.000 description 17
- 150000002367 halogens Chemical class 0.000 description 17
- 239000012299 nitrogen atmosphere Substances 0.000 description 17
- 229910052717 sulfur Inorganic materials 0.000 description 17
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 16
- 239000012298 atmosphere Substances 0.000 description 16
- 239000003153 chemical reaction reagent Substances 0.000 description 16
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 16
- 125000004434 sulfur atom Chemical group 0.000 description 16
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 16
- 238000010511 deprotection reaction Methods 0.000 description 15
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 15
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 15
- 150000007660 quinolones Chemical class 0.000 description 15
- HEMHJVSKTPXQMS-DYCDLGHISA-M Sodium hydroxide-d Chemical compound [Na+].[2H][O-] HEMHJVSKTPXQMS-DYCDLGHISA-M 0.000 description 14
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 14
- 125000002252 acyl group Chemical group 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 12
- 125000004185 ester group Chemical group 0.000 description 12
- 150000002148 esters Chemical group 0.000 description 12
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 12
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 12
- 229920006395 saturated elastomer Polymers 0.000 description 12
- XOQQVKDBGLYPGH-UHFFFAOYSA-N 2-oxo-1h-quinoline-3-carboxylic acid Chemical class C1=CC=C2NC(=O)C(C(=O)O)=CC2=C1 XOQQVKDBGLYPGH-UHFFFAOYSA-N 0.000 description 11
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 11
- 125000000304 alkynyl group Chemical group 0.000 description 11
- 150000001408 amides Chemical class 0.000 description 11
- 235000019270 ammonium chloride Nutrition 0.000 description 11
- 125000003118 aryl group Chemical group 0.000 description 11
- 230000003197 catalytic effect Effects 0.000 description 11
- 239000013078 crystal Substances 0.000 description 11
- 238000006460 hydrolysis reaction Methods 0.000 description 11
- 150000004702 methyl esters Chemical class 0.000 description 11
- 238000006722 reduction reaction Methods 0.000 description 11
- JUSOWTKVZJDEDG-IONNQARKSA-N 6,7-difluoro-1-[(1r,2s)-2-fluorocyclopropyl]-8-methoxy-4-oxoquinoline-3-carboxylic acid Chemical compound COC1=C(F)C(F)=CC(C(C(C(O)=O)=C2)=O)=C1N2[C@@H]1C[C@@H]1F JUSOWTKVZJDEDG-IONNQARKSA-N 0.000 description 10
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 10
- 201000010099 disease Diseases 0.000 description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 10
- 230000007062 hydrolysis Effects 0.000 description 10
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 10
- 238000002360 preparation method Methods 0.000 description 10
- 230000009467 reduction Effects 0.000 description 10
- 239000012047 saturated solution Substances 0.000 description 10
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 10
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical group [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
- 125000004494 ethyl ester group Chemical group 0.000 description 9
- 239000000843 powder Substances 0.000 description 9
- 238000007363 ring formation reaction Methods 0.000 description 9
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 8
- 206010034972 Photosensitivity reaction Diseases 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 229910052796 boron Inorganic materials 0.000 description 8
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 8
- 238000006352 cycloaddition reaction Methods 0.000 description 8
- 238000001035 drying Methods 0.000 description 8
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 8
- 150000003951 lactams Chemical class 0.000 description 8
- 239000003446 ligand Substances 0.000 description 8
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 8
- 239000002244 precipitate Substances 0.000 description 8
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 8
- 238000001953 recrystallisation Methods 0.000 description 8
- 238000006798 ring closing metathesis reaction Methods 0.000 description 8
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
- 235000017557 sodium bicarbonate Nutrition 0.000 description 8
- 125000000547 substituted alkyl group Chemical group 0.000 description 8
- HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 8
- TUYIHOJSSJJFMO-UHFFFAOYSA-N 2,3,4,5,6,6a-hexahydro-1h-cyclopenta[c]pyrrol-3a-amine Chemical class C1CCC2CNCC21N TUYIHOJSSJJFMO-UHFFFAOYSA-N 0.000 description 7
- 108010016626 Dipeptides Proteins 0.000 description 7
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 7
- FKCMADOPPWWGNZ-YUMQZZPRSA-N [(2r)-1-[(2s)-2-amino-3-methylbutanoyl]pyrrolidin-2-yl]boronic acid Chemical class CC(C)[C@H](N)C(=O)N1CCC[C@H]1B(O)O FKCMADOPPWWGNZ-YUMQZZPRSA-N 0.000 description 7
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 7
- 235000001014 amino acid Nutrition 0.000 description 7
- 229940024606 amino acid Drugs 0.000 description 7
- 150000001413 amino acids Chemical class 0.000 description 7
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 7
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 7
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- 239000012279 sodium borohydride Substances 0.000 description 7
- 229910000033 sodium borohydride Inorganic materials 0.000 description 7
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 7
- 238000010792 warming Methods 0.000 description 7
- UZHVXJZEHGSWQV-UHFFFAOYSA-N 1,2,3,3a,4,5,6,6a-octahydrocyclopenta[c]pyrrole Chemical group C1NCC2CCCC21 UZHVXJZEHGSWQV-UHFFFAOYSA-N 0.000 description 6
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 6
- 125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 description 6
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical group [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 230000005856 abnormality Effects 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 description 6
- 238000006482 condensation reaction Methods 0.000 description 6
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 6
- 239000002198 insoluble material Substances 0.000 description 6
- 239000012948 isocyanate Substances 0.000 description 6
- 150000002513 isocyanates Chemical class 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 6
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 6
- YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 5
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 5
- 238000006969 Curtius rearrangement reaction Methods 0.000 description 5
- 241000588724 Escherichia coli Species 0.000 description 5
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 5
- 239000013543 active substance Substances 0.000 description 5
- 239000000654 additive Substances 0.000 description 5
- 125000004849 alkoxymethyl group Chemical group 0.000 description 5
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 5
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 5
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 5
- 239000000460 chlorine Substances 0.000 description 5
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 5
- 125000006575 electron-withdrawing group Chemical group 0.000 description 5
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 5
- 210000003128 head Anatomy 0.000 description 5
- 150000002431 hydrogen Chemical class 0.000 description 5
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 5
- 150000003949 imides Chemical class 0.000 description 5
- 239000012528 membrane Substances 0.000 description 5
- RPZAAFUKDPKTKP-UHFFFAOYSA-N n-(methoxymethyl)-1-phenyl-n-(trimethylsilylmethyl)methanamine Chemical compound COCN(C[Si](C)(C)C)CC1=CC=CC=C1 RPZAAFUKDPKTKP-UHFFFAOYSA-N 0.000 description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 5
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 5
- IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 238000006462 rearrangement reaction Methods 0.000 description 5
- 239000012312 sodium hydride Substances 0.000 description 5
- 229910000104 sodium hydride Inorganic materials 0.000 description 5
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- C07D498/06—Peri-condensed systems
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- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
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- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/56—Ring systems containing three or more rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
- C07D491/048—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
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- Health & Medical Sciences (AREA)
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- Medicinal Chemistry (AREA)
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- Life Sciences & Earth Sciences (AREA)
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- Reproductive Health (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
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| EP2602253A4 (en) | 2010-08-06 | 2014-01-01 | Daiichi Sankyo Co Ltd | CRYSTAL OF AN ANTIBACTERIAL CONNECTION |
| TW201444558A (zh) * | 2013-03-15 | 2014-12-01 | Melinta Therapeutics Inc | 使用喹諾酮類抗生素治療淋病感染的方法 |
| LT3413892T (lt) | 2016-02-12 | 2022-06-10 | Cytokinetics, Incorporated | Tetrahidroizochinolino dariniai |
| MX2022004742A (es) * | 2019-10-23 | 2022-05-16 | Taigen Biotechnology Co Ltd | Derivados del acido carboxilico de quinolona. |
| KR20240141704A (ko) * | 2021-07-22 | 2024-09-27 | 더 텍사스 에이 & 엠 유니버시티 시스템 | 활성화된 페레이트 용액 및 이의 방법 |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0343524A1 (en) * | 1988-05-23 | 1989-11-29 | Shionogi Seiyaku Kabushiki Kaisha | Pyridonecarboxylic acids and antibacterial agents |
| WO1996023782A1 (en) * | 1995-02-02 | 1996-08-08 | Daiichi Pharmaceutical Co., Ltd. | Heterocyclic compounds |
| WO1996039407A1 (en) * | 1995-06-06 | 1996-12-12 | Abbott Laboratories | Quinolizinone type compounds |
| EP0812838A1 (en) * | 1994-02-04 | 1997-12-17 | Dainippon Pharmaceutical Co., Ltd. | Pyridonecarboxylic acid derivative substituted by bicyclic amino group, ester thereof, salt thereof, and bicyclic amine as intermediate therefor |
| RU2248970C2 (ru) * | 1998-11-24 | 2005-03-27 | Дайити Фармасьютикал Ко., Лтд. | Циклоалкилзамещенные производные аминометилпирролидина и антибактериальный агент на их основе |
| WO2005049602A1 (en) * | 2003-11-18 | 2005-06-02 | Warner-Lambert Company Llc | Quinolone antibacterial agents |
| RU2276154C2 (ru) * | 2000-11-24 | 2006-05-10 | Мейдзи Сейка Кайся, Лтд. | Производные карбапенема, применение их для изготовления фармацевтической композиции, фармацевтическая композиция на их основе и способ лечения и/или профилактики инфекционных заболеваний |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61282382A (ja) | 1985-06-06 | 1986-12-12 | Dainippon Pharmaceut Co Ltd | フエニル置換１，８−ナフチリジン誘導体、そのエステルおよびその塩 |
| EP0242789A3 (en) | 1986-04-25 | 1990-09-05 | Dainippon Pharmaceutical Co., Ltd. | Novel quinoline derivates and processes for preparation thereof |
| JPH0676400B2 (ja) * | 1987-08-25 | 1994-09-28 | 大日本製薬株式会社 | 新規ピリドンカルボン酸誘導体、そのエステルおよびその塩 |
| MY105136A (en) | 1988-04-27 | 1994-08-30 | Daiichi Seiyaku Co | Optically active pyridonecarboxylic acid derivatives. |
| JP2807277B2 (ja) | 1988-08-31 | 1998-10-08 | 第一製薬株式会社 | スピロ化合物 |
| JPH0278659A (ja) * | 1988-09-12 | 1990-03-19 | Shionogi & Co Ltd | アザビシクロアルカン類化合物 |
| WO1994014794A1 (fr) | 1992-12-28 | 1994-07-07 | Yoshitomi Pharmaceutical Industries, Ltd. | Derive d'acide 8-methoxyquinolonecarboxylique |
| JPH06345261A (ja) | 1993-04-16 | 1994-12-20 | Daihen Corp | 自動搬送装置の搬送用ハンド |
| DE4435479A1 (de) | 1994-10-04 | 1996-04-11 | Bayer Ag | Chinolon- und Naphthyridoncarbonsäure-Derivate |
| JP4132155B2 (ja) * | 1996-10-25 | 2008-08-13 | 第一三共株式会社 | 三環性アミン誘導体 |
| US7563805B2 (en) * | 2005-05-19 | 2009-07-21 | Daiichi Pharmaceutical Co., Ltd. | Tri-, tetra-substituted-3-aminopyrrolidine derivative |
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2008
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2009
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2013
- 2013-09-30 CY CY20131100845T patent/CY1114444T1/el unknown
- 2013-11-19 US US14/084,485 patent/US20140142096A1/en not_active Abandoned
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0343524A1 (en) * | 1988-05-23 | 1989-11-29 | Shionogi Seiyaku Kabushiki Kaisha | Pyridonecarboxylic acids and antibacterial agents |
| EP0812838A1 (en) * | 1994-02-04 | 1997-12-17 | Dainippon Pharmaceutical Co., Ltd. | Pyridonecarboxylic acid derivative substituted by bicyclic amino group, ester thereof, salt thereof, and bicyclic amine as intermediate therefor |
| WO1996023782A1 (en) * | 1995-02-02 | 1996-08-08 | Daiichi Pharmaceutical Co., Ltd. | Heterocyclic compounds |
| WO1996039407A1 (en) * | 1995-06-06 | 1996-12-12 | Abbott Laboratories | Quinolizinone type compounds |
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